Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, THU-PKU Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, THU-PKU Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China; PKU-THU Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.
Mol Cell. 2016 Sep 15;63(6):1066-79. doi: 10.1016/j.molcel.2016.08.032.
Polycomb group proteins and the related histone modification H3K27me3 can maintain the silencing of key developmental regulators and provide cellular memory. However, how such an epigenetic state is reprogrammed and inherited between generations is poorly understood. Using an ultra-sensitive approach, STAR ChIP-seq, we investigated H3K27me3 across 14 developmental stages along mouse gametogenesis and early development. Interestingly, highly pervasive H3K27me3 is found in regions depleted of transcription and DNA methylation in oocytes. Unexpectedly, we observed extensive loss of promoter H3K27me3 at Hox and other developmental genes upon fertilization. This is accompanied by global erasure of sperm H3K27me3 but inheritance of distal H3K27me3 from oocytes. The resulting allele-specific H3K27me3 patterns persist to blastocysts before being converted to canonical forms in postimplantation embryos, where both H3K4me3/H3K27me3 bivalent promoter marks are restored at developmental genes. Together, these data revealed widespread resetting of epigenetic memory and striking plasticity of epigenome during gametogenesis and early development.
多梳蛋白组蛋白和相关的组蛋白修饰 H3K27me3 可以维持关键发育调节剂的沉默，并为细胞提供记忆。然而，这种表观遗传状态如何在代际之间重新编程和遗传尚不清楚。我们使用超灵敏的 STAR ChIP-seq 方法研究了沿小鼠配子发生和早期发育的 14 个发育阶段的 H3K27me3。有趣的是，在卵母细胞中，高度普遍的 H3K27me3 存在于转录和 DNA 甲基化缺失的区域。出乎意料的是，我们观察到受精后 Hox 和其他发育基因的启动子 H3K27me3 大量丢失。这伴随着精子 H3K27me3 的全局擦除，但卵母细胞从远端继承 H3K27me3。在被转化为植入后胚胎中的典型形式之前，由此产生的等位基因特异性 H3K27me3 模式在囊胚中持续存在，其中在发育基因处恢复了 H3K4me3/H3K27me3 双价启动子标记。总之，这些数据揭示了在配子发生和早期发育过程中广泛的表观遗传记忆重置和表观基因组的惊人可塑性。
